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AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.